Pharmacological modification of endogenous antioxidant enzymes by ursolic acid on tetrachloride-induced liver damage in rats and primary cultures of rat hepatocytes

The purpose of this study was to investigate possible protective effects of ursolic acid against CCl4-induced alterations of antioxidant defence enzymes in vivo as well as its effects against CCl4-intoxication in vitro. Pre-treatment of rats with ursolic acid significantly reduced serum levels of gl...

Full description

Saved in:
Bibliographic Details
Published in:Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie 2001-06, Vol.53 (2-3), p.199-206
Main Authors: MARTIN-ARAGON, S, DE LAS HERAS, B, SANCHEZ-REUS, M. I, BENEDI, J
Format: Article
Language:English
Subjects:
Alanine Transaminase - metabolism
Animals
Antioxidants - pharmacology
Aspartate Aminotransferases - metabolism
Biological and medical sciences
Carbon Tetrachloride - toxicity
Catalase - metabolism
Cell Survival - drug effects
Cells, Cultured
Chemical and Drug Induced Liver Injury - blood
Chemical and Drug Induced Liver Injury - prevention & control
Digestive system
Dose-Response Relationship, Drug
Glutathione - metabolism
Glutathione Peroxidase - metabolism
Glutathione Reductase - metabolism
Hepatocytes - cytology
Hepatocytes - drug effects
Hepatocytes - enzymology
Hydroxyl Radical - metabolism
Lipid Peroxidation - drug effects
Liver - drug effects
Liver - enzymology
Medical sciences
Pharmacology. Drug treatments
Random Allocation
Rats
Superoxide Dismutase - metabolism
Triterpenes - pharmacology
Ursolic Acid
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The purpose of this study was to investigate possible protective effects of ursolic acid against CCl4-induced alterations of antioxidant defence enzymes in vivo as well as its effects against CCl4-intoxication in vitro. Pre-treatment of rats with ursolic acid significantly reduced serum levels of glutamate-oxalate-transaminase and glutamate-pyruvate-transaminase previously increased by administration of CCl4. Treatment with ursolic acid also significantly reversed the decreased superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase activities and glutathione levels in the liver, as the concentration of reduced glutathione was increased and the content of oxidized glutathione decreased in ursolic acid treated groups. Levels of lipid peroxidation were higher in the CCl4 group but the increase was also reduced after drug treatment (p < 0.01 for 1, 2.5 and 5 mmol/kg). In vitro results indicated that addition to the culture medium of ursolic acid (p < 0.01 for 500 microM) resulted in a reduction of glutamate-oxalate-transaminase, lactate dehydrogenase activities and in a good survival rate for the CCl4-intoxicated hepatocytes. Ursolic acid also ameliorated lipid peroxidation in primary cultured rat hepatocytes exposed to CCl4, as demonstrated by a reduction in malondialdehyde production. Moreover, ursolic acid (50-500 microM) showed radical scavenging properties in terms of hydroxyl formation. The results obtained suggest that ursolic acid treatment can normalize the disturbed antioxidant status of rats intoxicated with CCl4 by maintaining the levels of glutathione and by inhibiting the production of malondialdehyde due to its radical scavenging properties.
ISSN:0940-2993
1618-1433
DOI:10.1078/0940-2993-00185